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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-sanchis Pedro AAvila-López Iva Tic David Valle-García Marta Ribalta-Vilella Luis Labrador deb Ranjan Banerjee Ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(saMP8)control mice and saMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the saMP8 group treated with G9a inhibitor than in the saMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG saMP8

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Microcephaly prevalence after the 2015 to 2016 Zika outbreak in Tangará da Serra, Brazil: a population-based study

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Reproductive and developmental Medicine 2022年第2期6卷 98-103页

作者： Juliana Herrero da Silva Ana Claudia Pereira Tercas-Trettel Juliano Andre Boquett Giovanny Vinicius Araujo Franca Augusto Cesar Cardoso-dos-santos Marina Atanaka Marcelo Zagonel Oliveira Anna Pires Terra Viviane Karoline Vivi Lucia Andreia Nunes de Oliveira Lucia Schaedler Ronaldo Fernandes santos Alves Lavinia Schuler-Faccini Prefeitura municipal de Tangara da Serra Secretaria de SaudeVigilancia EpidemiologicaTangara da SerraBrazil Programa de Pos-Graduacao em Genetica e Biologia Molecular Universidade Federal do Rio Grande do SulPorto AlegreBrazil Universidade do Estado de Mato Grosso Tangara da SerraBrazil Programa de Pos-Graduagcao em saude Coletiva Universidade Federal de Mato GrossoCuiabaBrazil Instituto Nacional de Genetica Medica Populacional-INaGeMP Servico de Genetica MedicaHospital de Clinicas de Porto Alegre(HCPA)Porto AlegreBrazil Programa de Pos-Graduacao em saude da Crianga e do Adolescente Universidade Federal do Rio Grande do SulPorto AlegreBrazil secretaria de Vigilancia em saude Ministerio da SaudeBrasiliaBrazil Laboratorio de Visualizacao Avangada e Geoinformatica(VIZLab) Programa de Pos-Graduacao em Computacao AplicadaUniversidade do Vale do Rio dos SinosSao LeopoldoBrazil Programa de Pos-Graduacao em Ciencia da Informacao Universidade Federal do Rio Grande do SulPorto AlegreBrazil Clinica santa Luzia Tangara da SerraBrazil

Objective::Prenatal infection with the Zika virus (ZIKV) can lead to congenital Zika syndrome (CZS), characterized by microcephaly and brain injury. However, there are questions regarding the prevalence of microcephaly/CZS after the ZIKV outbreak in defined geographic areas. This study aimed to identify adverse outcomes in live births of fetuses exposed in utero to the ZIKV, compared to unexposed births, as well as maternal sociodemographic, delivery, and birth ***::Here, we conducted a cross-sectional observational study to investigate the characteristics of all live births in the city of Tangará da Serra, Mato Grosso, Brazil, in 2016, after the outbreak of ZIKV infection in late 2015. All live births of children to women residing in the municipality of Tangará da Serra between January 1 and december 31, 2016, were evaluated, and head circumference was measured at birth and after 24 hours. Children born with microcephaly or a maternal history of confirmed or suspected prenatal ZIKV infection were evaluated by a multidisciplinary team. The outcomes of the exposed and non-exposed children were compared. Prevalence ratios and their respective 95% confidence intervals were calculated for sociodemographic, delivery, and live birth ***::Of 1,441 live births, 106 (7.3%) were from mothers with confirmed or highly probable exposure to ZIKV. The prevalence of severe congenital microcephaly (41.7/10,000) in Tangará da Serra in 2016 was ten-fold higher than that in Latin America before ***::This study may serve as a model to investigate possible outbreaks of infections in a defined geographical space in the future.

关键词： Epidemiology Live births Microcephaly Zika virus

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The Igarape Weir decelerated transport of contaminated sediment in the Paraopeba River after the failure of the B1 tailings dam(Brumadinho)

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International Journal of Sediment Research 2023年第5期38卷 673-697页

作者： Daniela Patrícia salgado Terêncio Fernando António Leal Pacheco Renato Farias do Valle Junior Maytê Maria Abreu Pires de Melo Silva Teresa Cristina Tarlé Pissarra Marília Carvalho de Melo Carlos Alberto Valera Luís Filipe sanches Fernandes Inov4Agro/Centro de Investiga??o e Tecnologias Agroambientais e Biológicas Universidade de Trás-os-Montes e Alto Douro Centro de Química de Vila Real Universidade de Trás-os-Montes e Alto Douro Faculdade de Ciências Agrárias e Veterinárias Universidade Estadual Paulista(UNESP) Via de Acesso Prof.Paulo Donato Castellane Instituto Federal do Triangulo Mineiro Campus Uberaba Laboratório de Geoprossessamento 5. Secretaria de Estado de Meio Ambiente e Desenvolvimento Sustentável Cidade Administrativa do Estado de Minas Gerais Rodovia Jo?o Paulo II 6. Coordenadoria Regional das Promotorias de Justi?a do Meio Ambiente das Bacias dos Rios Paranaíba e Baixo Rio Grande Rua Coronel Ant?nio Rios

The B1 dam of Co rrego do Feij～ao Mine, owned by Vale, S.A. mining company and located on the FerroCarv～ao stream, collapsed and injected 2.8 Mm3of clayey, silty, and sandy iron-and manganese-rich tailings into the Paraopeba River(Minas Gerais state, Brazil). The accident occurred on 25 January2019 and the tailings have been co-transported with coarser natural sediment since then, being partly trapped in the Igarape Weir reservoir located on the Paraopeba River nearly 45 km downstream the injection point. The general purpose of the current study was to model suspended sediment transport in the vicinity of the Igarape Weir aiming to assess the concomitant barrier effect imposed by this ***, the spatial distributions of suspended clay, silt, and very fine-grained sand fractions(CSS) of sediment were mapped around the Igarape Weir under low-flow(16 m3/s) and high-flow(5 to 10,000years return period stream discharge; 699—2,699 m3/s) regimes, using RiverFlow2D as the modelling tool. The concentrations of the various grain materials in the upstream and downstream sectors were quantified linking the barrier effect to concentration reductions in the direction of stream flow. It was also a study goal to calculate differences of iron and manganese concentrations in the sediment + tailings mixtures along the Paraopeba River. The study results showed reductions in the CSS between 6.6% and18%, from upstream to downstream of the Igarape Weir, related with backwater effects, free and submerged hydraulic jumps, bank sedimentation in periods of high flow, and streambed sedimentation controlled by channel sinuosity and tailings density. These reductions were accompanied by drops in the concentrations of iron and manganese present in the clay and silt fractions, which varied between 6% and42% under low flows and between 16% and 44% under high flows. Bank sedimentation was viewed as a potential threat to the riparian vegetation in the long-term. Dredging is the poten

关键词： Sediment transport Tailings dam break Metal contamination Hydrodynamic modelling RiverFlow2D Ratio concentration analysis

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Vegetation structure and edaphic factors in veredas reflect different conservation status in these threatened areas

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Forest Ecosystems 2022年第3期9卷 387-395页

作者： Yule Roberta Ferreira Nunes Camila Silveira Souza Islaine Francielly Pinheiro de Azevedo Odirlei Simôes de Oliveira Leidivan Almeida Frazão Rúbia santos Fonseca Rubens Manoel dos santos Walter Viana Neves Programa de Pós-Graduaçao Em Botânica Aplicada Departamento de Biologia GeralUniversidade Estadual de Montes ClarosAvenida Dr.Ruy BragaS/N-Bairro Vila MauricéiaMontes ClarosMinas Gerais39401-089Brazil Laboratório de Ecologia Vegetal Universidade Estadual de Montes ClarosAvenida Dr.Ruy BragaS/N-Bairro Vila MauricéiaMontes ClarosMinas Gerais39401-089Brazil Instituto de Ciências Agrarias-Universidade Federal de Minas Gerais Avenida Universitária1.000-Bairro Universit�arioMontes ClarosMinas Gerais39404-547Brazil departamento de Ciências Florestais Universidade Federal de LavrasCP 3037LavrasMinas Gerais37200-000Brazil Instituto Mineiro de Gestao dasÁguas Secretaria de Estado de Meio Ambiente e Desenvolvimento SustentávelAvenida JoséCorreia Machado900-Bairro IbiturunaMontes ClarosMinas Gerais39401-832Brazil

Background:In Cerrado humid areas,veredas are considered as hygrophilous communities,marked by the presence of the Mauritia flexuosa palm tree emerging in the wetter *** in veredas ecosystems due to drought and changes in the water table,which represent important areas for biodiversity maintenance in the Brazilian cerrado,can lead to the emergence of new landscapes and *** that the veredas are changed in species composition due to anthropogenic factors,in this study,we evaluated the flora composition and described the current vegetation profile of two veredas under different disturbances levels that are located in the north of Minas Gerais State,***:Altogether,2,268 individuals of 91 species belonging to 36 families were *** results demonstrated that the studied veredas were floristically different in terms of the arboreous-shrubby species composition,richness,and *** the hygrophilous forest formations and open areas in the two veredas present typical species from these environments(same species with high importance values),the drought in the water table caused an expansion of Cerrado species in the open areas and in the hygrophilous ***,in the hygrophilous forest there was an increase in the abundance of species that occur in less saturated ***:Our results demonstrate that the studied veredas are changing in species composition due to anthropogenic factors which leads to the drought of these formations(water balance effect).These anthropogenic effects cause a modification with the expansion and increase in the abundance of typical species of other areas of Cerrado and resistant to less saturated soils,leading to the veredas ***,future studies should investigate other veredas on a broader scale to detect changes in the water table that lead to a consequent change in vegetation *** this way,we will have support for the conscientious management and conservatio

关键词： Cerrado Conservation Palm swamp Plant distribution Climate change Water balance effect Vereda drought Phytosociological analysis

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Extracellular vesicles from oviductal and uterine fluids supplementation in sequential in vitro culture improves bovine embryo quality

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Journal of Animal Science and Biotechnology 2023年第1期14卷 114-133页

作者： Cláudia Lima Verde Leal Karina Canón-Beltrán Yulia N.Cajas Meriem Hamdi Aracelli Yaryes María Gemma Millán de la Blanca Paula Beltrán-Brena Rosane Mazzarella Juliano Coelho da Silveira Alfonso Gutiérrez-Adán Encina M González Dimitrios Rizos department of Animal Reproduction National Center Institute for Agriculture and Food Research and Technology(CSIC-INIA)28040 MadridSpain. departamento de Medicina Veterinaria Faculdade de Zootecnia e Engenharia de AlimentosUniversidade de Sao Paulo(FZEA-USP)PirassunungaBrazil. Facultad de Ciencias Agrarias y Ambientales Programa de Medicina VeterinariaFundacion Universitaria Juan de CastellanosTunjaColombia. Laboratorio de Biotecnologia de la Reproduccion Animal Facultad de Ciencias AgropecuariasUniversidad de Cuenca(UC)EC010205 CuencaEcuador. department of Anatomy and Embryology Veterinary Faculty-Universidad Complutense de Madrid(UCM)MadridSpain.

Background:In vitro production of bovine embryos is a well-established technology,but the in vitro culture(IVC)system still warrants improvements,especially regarding embryo *** study aimed to evaluate the effect of extracellular vesicles(EVs)isolated from oviductal(OF)and uterine fluid(UF)in sequential IVC on the development and quality of bovine *** were cultured in SOF supplemented with either Bsa or EVs-depleted fetal calf serum(dFCS)in the presence(Bsa-EV and dFCS-EV)or absence of EVs from OF(D1 to D4)and UF(D5 to D8),mimicking in vivo *** from oviducts(early luteal phase)and uterine horns(mid-luteal phase)from slaughtered heifers were isolated by size exclusion *** rate was recorded on days 7-8 and their quality was assessed based on lipid contents,mitochondrial activity and total cell numbers,as well as survival rate after *** mRNA abundance for lipid metabolism-related transcripts and levels of phosphorylated hormonesensitive lipase(pHSL)proteins were also ***,the expression levels of 383 miRNA in OF-and UF-EVs were assessed by ***:Blastocyst yield was lower(Psa treatments compared with dFCS *** rates after vitrification/warming were improved in dFCS-EVs(Psa-EV compared with respective controls(dFCS and Bsa),while lipid content was decreased in dFCSEV(P0.05).Lipid metabolism transcripts were affected by EVs and showed interaction with type of protein source in medium(PPARGC1B,LDLR,CD36,FASN and PNPLA2,Pdevelopment but improves blast

关键词： Cattle Cryopreservation Embryo development Exosomes Lipid metabolism miRNAs Oviduct Uterus

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Polyphenols as potential enhancers of stem cell therapy against neurodegeneration

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Neural Regeneration Research 2022年第10期17卷 2093-2101页

作者： Diana Rodríguez-Vera Antonio Abad-García Nancy Vargas-Mendoza Rodolfo Pinto-Almazán Eunice D.Farfán-García José A.Morales-González Marvin A.Soriano-Ursúa Sección de Estudios de Posgrado e Investigación.Escuela Superior de Medicina Instituto Politécnico NacionalMéxico CityMéxico Unidad de Investigación Hospital Regional de Alta Especialidad IxtapalucaCarretera Federal México-Puebla km 34.5State of MéxicoMéxico

The potential of polyphenols for treating chronic-degenerative diseases(particularly neurodegenerative diseases)is ***,the selection of the best polyphenol for each treatment,the mechanisms by which they act,and their efficacy are frequently *** this review,the basics and the advances in the field,as well as suggestions for using natural and synthetic polyphenols alone or in a combinatorial strategy with stem cell assays,are compiled and ***,stem cells exhibit several responses when polyphenols are added to their environment,which could provide us with knowledge for advancing the elucidation of the origin of *** also,polyphenols are being included in the innovative strategies of novel therapies for treating neurodegenerative diseases as well as metabolic diseases related to *** this regard,flavonoid compounds are suggested as the best natural polyphenols due to their several mechanisms for acting in ameliorative effects;but increasing reports are involving other *** if some facts limiting bioactivity prevent them from conventional use,some natural polyphenols and derivatives hold the promise for being improved compounds,judged by their induced *** current results suggest polyphenols as enhancers of stem cell therapy against the targeted diseases.

关键词： Alzheimer’s disease chronic degenerative diseases combinatorial therapy metabolism neurodegenerative diseases neuronal damage neuroprotection Parkinson’s disease polyphenols stem cell assays

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Role of lysophosphatidic acid and its receptors in health and disease:novel therapeutic strategies

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Signal Transduction and Targeted Therapy 2021年第3期6卷 630-647页

作者： Luiz Henrique Medeiros Geraldo Tania Cristina Leite de sampaio Spohr Rackele Ferreira do Amaral Anna Carolina Carvalho da Fonseca Celina Garcia Fabio de Almeida Mendes Catarina Freitas Marcos Fabio dossantos Flavia Regina Souza Lima Institute de Ciencias BiomedicasUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil Universite de Paris PARCCINSERMF-75015 ParisFrance Institute Estadual do Cerebro Paulo Niemeyer-secretaria de Estado de saude Rio de JaneiroBrazil Instituto de saiide de Nova Friburgo Universidade Federal Fluminense28625-650 Nova FriburgoBrazil

Lysophosphatidic acid(LPA)is an abundant,bioactive phospholipid,with multiple functions both in development and in pathological ***,we review the literature about the differential signaling of LPA through its specific receptors,which makes this lipid a versatile signaling *** differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis;and also,how it can act as a powerful mediator of pathological conditions,such as neuropathic pain,neurodegenerative diseases,and cancer ***,we review the preclinical and clinical uses of Autotaxin,LPA,and its receptors as therapeutic targets,approaching the most recent data of promising molecules modulating both LPA production and *** review aims to summarize the most update knowledge about the mechanisms of LPA production and signaling in order to understand its biological functions in the central nervous system both in health and disease.

关键词： therapeutic clinical diseases

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The largest dengue outbreak in Argentina and spatial analyses of dengue cases in relation to a control program in a district with sylvan and urban environments

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Asian Pacific Journal of Tropical Medicine 2018年第3期11卷 227-234页

作者： Aníbal E Carbajo Alejandra Rubio María J Viani María R Colombo Laboratorio de Eoclogía de Enfermedades Transmitidas por Vectores Instituto de Investigación e Ingeniería AmbientalUniversidad Nacional de General San Martín Consejo Nacional de Investigaciones Científicas y Técnicas secretaria de Política sanitaria y desarrollo Humano Municipio de Tigre

Objective: To analyze the largest outbreak of dengue in Argentina in the municipality of Tigre during 2016, through detailed spatial analyses of the occurrence of cases in relation to demographic factors and vector control actions. Methods: detailed and georreferenced data on dengue cases with laboratory results(NS1 or IgM) were analyzed. The occurrences of imported and autochthonous cases by census tract were modeled using demographic variables(population by age class, proportion of foreigners, proportion with university grade, proportion of males), dwelling variables(number of homes, proportion of dwellings with latrine, number of dwellings, proportion of houses, proportion of flats, proportion of slums) and census tract area as explanatory variables. The probability of occurrence of autochthonous and imported cases was modeled separately. The spatio-temporal occurrence of cases was studied in relation to focal and perifocal control actions(involving education campaigns, removal of Aedes aegypti breeding sites and exhaustive insecticide spraying) to assess the efficiency in stopping autochthonous cases spreading. Results: All autochthonous cases occurred in the urban environment with no sylvan cases. The majority of the imported cases registered came from Paraguay and Northeastern Argentina. The age structure of imported and autochthonous cases did not differ from the age structure of the municipality, while that of the negative cases *** studied spatially, the occurrence of imported cases by census tract was mildly associated with a higher proportion of foreign population and more people at active age, while occurrence of autochthonous cases was not significantly associated with any of the studied *** census tracts with laboratory confirmed results, the models showed higher probability of autochthonous cases related to higher population density and population age structure. The clustering of autochthonous cases was generally mild, with prevailing i

关键词： Aedes aegypti Vector-borne diseases Vector control dengue epidemic

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Higher-Dose Primaquine to Prevent Relapse of Plasmodium vivax Malaria

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四川生理科学杂志 2022年第2期44卷 347-347页

作者： Nathália N Chamma-Siqueira From Instituto Evandro Chagas Ministério da Saúde do Brasil Ananindeua (N.N.C-.S. S.P.S. G.M.R.V.) Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários (N.N.C.-S. E.J.M.S. F.P.C. G.M.R.V.) and Laboratório de Genética de Doenças Complexas (E.J.M.S. F.P.C.) Instituto de Ciências Biológicas and Laboratório de Farmacocinética de Drogas Antimaláricas Instituto de Ciências da Saúde (L.W.P.S. A.G.N.C.-M.) Universidade Federal do Pará Belém Secretaria de Saúde do Estado do Acre Cruzeiro do Sul (S.C.N. S.F.) and Grupo Técnico da Malária Coordenação-Geral de Vigilância de Zoonoses e Doenças de Transmissão Vetorial Departamento de Imunização e Doenças Transmissíveis Secretaria de Vigilância em Saúde Ministério da Saúde (P.B.M.) and Diretoria de Vigilância Epidemiológica Subsecretaria de Vigilância em Saúde Secretaria Estadual de Saúde do Distrito Federal (C.R.L.P.) Brasília - all in Brazil Epidemic Intelligence Service Center for Surveillance Epidemiology and Laboratory Services (S.-B.B.) and the Malaria Branch Division of Parasitic Diseases and Malaria Center for Global Health Centers for Disease Control and Prevention (S.-B.B. A.M.O.) - both in Atlanta and Instituto de Investigaciones en Ciencias Biomedicas Universidad Ricardo Palma Lima and Instituto de Enfermedades Tropicales Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas Chachapoyas (S.M.C.) - both in Peru.

Background:In most of the Americas,the recommended treatment to prevent relapse of Plasmodium vivax malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight,despite evidence of only moderate ***:In this trial conducted in Brazil,we evaluated three primaquine regimens to prevent relapse of *** malaria in children at least 5 years of age and in adults with microscopy-confirmed *** *** the patients received directly observed chloroquine for 3 days(total dose,25 mg per kilogram).Group 1 received a total primaquine dose of 3.5 mg per kilogram(0.5 mg per kilogram per day)over 7 days with unobserved administration;group 2 received the same regimen as group 1 but with observed administration;and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days(also 0.5 mg per kilogram per day)with observed *** monitored the patients for 168 days.

关键词： vivax Malaria regimen

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Arylated analogues of cypronazole: fungicidal effect and activity on human fibroblasts. Docking analysis and molecular dynamics simulations

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Natural Products and Bioprospecting 2022年第1期12卷 107-120页

作者： Natividad Herrera Cano Sebastian A.Andujar Cristina Theoduloz Daniel A.Wunderlin Ana N.santiago Guillermo Schmeda-Hirschmann Ricardo D.Enriz Gabriela E.Feresin Instituto de Biotecnología Facultad de IngenieríaUniversidad Nacional de San JuanCONICET-CCT San JuanAv.Libertador General San Martín1109(O)5400 San JuanArgentina Facultad de Química Bioquímica y Farmacia-IMIBIO-SL(CONICET)Universidad Nacional de San LuisChacabuco 9155700 San LuisArgentina Laboratorio de Cultivo Celular Facultad de Ciencias de la SaludUniversidad de TalcaCasilla 7473460000 TalcaChile ICYTAC CONICET and Universidad Nacional de CórdobaFacultad de Ciencias QuímicasDepartamentoQuímica OrgánicaCiudad UniversitariaBv.Juan Filloy s/n5000 CórdobaArgentina INFIQC CONICET and Universidad Nacional de CórdobaFacultad de Ciencias QuímicasDepartamento Química OrgánicaCiudad UniversitariaHaya de La Torre S/N5000 CórdobaArgentina Laboratorio de Química de Productos Naturales Instituto de Química de Recursos NaturalesUniversidad de TalcaCasilla 7473460000 TalcaChile

Triadimefon(TDM)and cyproconazole(CPZ)are two triazoles widely used as *** azoles were synthe-sised starting from commercial TDM and *** compounds were evaluated against phytopathogenic filamentous fungi,including Aspergillus fumigatus(AF),***(AN),***(AU),***(AJ),***(AT),Fusarium oxyspo-rum and Botrytis cinerea isolated from grapevine in the province of san Juan,*** of the synthesised compounds(1-(Biphenyl-4-yloxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one,1;2-(Biphenyl-4-yl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,3;3-Cyclopropyl-2-(4’-fluorobiphenyl-4-yl)-1-(1H-1,2,4-triazol1-yl)butan-2-ol,4)presented remarkable in vitro fungicidal properties,with better effects than TDM and CPZ on some of the target *** was assessed using human lung fibroblasts *** 1,with IC50 values of 389.4μM,was less toxic towards MRC-5 human lung fibroblasts than commercial TDM(248.5μM)and CPZ(267.4μM).Docking analysis and molecular dynamics simulations suggest that the compounds present the same interaction in the binding pocket of the CYP51B enzyme and with the same amino acids as *** derivatives investigated could be considered broad-spectrum but with some selectivity towards imperfect fungi.

关键词： Azoles Antifungal cytotoxicity Conformational and electronic analysis

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